2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Heterozygous loss-of-function variants in IFT140 are associated with polycystic kidney disease

Heterozygous loss-of-function variants in IFT140 are associated with polycystic kidney disease
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The study investigated the association between IFT140 loss-of-function (LoF) variants and polycystic kidney disease (PKD). The researchers reviewed cases of individuals who underwent genetic testing using a renal gene panel between May 2020 and December 2021. They identified 163 individuals with heterozygous predicted LoF IFT140 variants, of which 110 cases had a cystic phenotype. Among the remaining patients, diagnostic findings were discovered in cystic disease-associated genes or unrelated molecular diagnoses. The study found that 78 unique IFT140 truncating variants were identified, with 62% of these variants not reported in the general population. The most commonly reported CKD stages among the individuals were CKD3 (49.4%) and CKD2 (22.1%). In patients aged 65 and older, the majority had CKD stage 3 or lower, suggesting a milder phenotype association with IFT140. The table provided in the document shows the commonly identified IFT140 LoF variants and their frequencies in the general population. The conclusions of the study indicate that IFT140 LoF variants are associated with mild PKD phenotypes and forms of chronic kidney disease (CKD). The authors suggest that future studies with larger cohorts and investigations into the role of missense variants will help clarify the mechanism of PKD development and the prognosis for individuals carrying these variants. The introduction provides background information on ADPKD and the genes associated with the disease. It also highlights the role of IFT140 LoF variants in atypical ADPKD. The methods section describes the cases included in the analysis and how patient phenotypes were determined. The results section presents the findings of the study, including the number of individuals with IFT140 variants and their clinical information. Overall, the study provides evidence supporting the involvement of IFT140 Loss-of-Function variants in PKD and suggests that these variants may be associated with milder forms of the disease. Further research with larger cohorts is needed to gain a better understanding of the mechanism and prognosis related to IFT140 variants in PKD.

Asset Subtitle

Submitter Only - Nour Baddar, PhD; Co-Author - Dinah Clark, MS; Co-Author - Karen Phaik Har Lim, PhD; Co-Author - Lili Li, MD, PhD; Co-Author - Lisa Vincent, PhD, FACMG; Co-Author - Jing Xie, PhD; Co-Author - Yuan Xue, PhD, FACMG; Presenting Author - Sumit Punj, PhD, FACMG;

Meta Tag

Genetic Testing

NextGen Sequencing

Variant Detection

Co-Author Dinah Clark, MS

Co-Author Karen Phaik Har Lim, PhD

Co-Author Lili Li, MD, PhD

Co-Author Lisa Vincent, PhD, FACMG

Co-Author Jing Xie, PhD

Co-Author Yuan Xue, PhD, FACMG

Presenting Author Sumit Punj, PhD, FACMG

Submitter Only Nour Baddar, PhD

Keywords

IFT140 loss-of-function variants

polycystic kidney disease

genetic testing

renal gene panel

cystic phenotype

cystic disease-associated genes

CKD stages

mild PKD phenotypes

chronic kidney disease

ADPKD